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Clinical significance and gene expression study of human hepatic stellate cells in HBV related-hepatocellular carcinoma.

Journal of experimental & clinical cancer research : CR (2013-04-23)
Rui Liao, Han Wu, Yong Yi, Jia-Xing Wang, Xiao-Yan Cai, Hong-Wei He, Yun-Feng Cheng, Jian Zhou, Jia Fan, Jian Sun, Shuang-Jian Qiu
ABSTRACT

Peritumoral activated hepatic stellate cells (HSCs) are versatile myofibroblast-like cells closely related with hepatocellular carcinoma (HCC) progression. So far, comprehensive comparison of gene expression of human HSCs during hepatocarcinogenesis is scanty. Therefore, we identified the phenotypic and genomic characteristics of peritumoral HSCs to explore the valuable information on the prognosis and therapeutic targets of HBV related HCC. A tissue microarray containing 224 HBV related HCC patients was used to evaluate the expression of phenotype markers of HSCs including α-SMA, glial fibrillary acidic protein (GFAP), desmin, vinculin and vimentin. HSCs and cancer associated myofibroblasts (CAMFs) were isolated from normal, peritumoral human livers and cancer tissues, respectively. Flow cytometry and gene microarray analysis were performed to evaluate the phenotypic changes and gene expression in HCC, respectively. Peritumoral α-SMA positive HSCs showed the prognostic value in time to recurrence (TTR) and overall survival (OS) of HCC patients, especially in early recurrence and AFP-normal HCC patients. Expression of GFAP positive HSCs cell lines LX-2 was significantly decreased after stimulation with tumor conditioned medium. Compared with quiescent HSCs, peritumoral HSCs and intratumoral CAMFs expressed considerable up- and down-regulated genes associated with biological process, cellular component, molecular function and signaling pathways involved in fibrogenesis, inflammation and progress of cancer. Peritumoral activated HSCs displayed prognostic value in HBV related-HCC, and their genomic characteristics could present rational biomarkers for HCC risk and promising therapeutic targets.

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LX-2 Human Hepatic Stellate Cell Line, The LX-2 human hepatic stellate cell line has been extensively characterized and retain key features of hepatic stellate cytokine signaling, neuronal gene expression, retinoid metabolism, and fibrogenesis, making them a highly suitable model of human hepatic fibrosis.